A new theory called the Adipokine Hypothesis explains how a common type of heart failure may begin.
This type is called heart failure with preserved ejection fraction, or HFpEF. The idea is that the problem starts not in the heart, but in the fat inside the body.
The paper was published in the Journal of the American College of Cardiology (JACC) and presented at a major heart conference in 2025. Dr. Milton Packer, a heart expert from Baylor University Medical Center and Imperial College in London, wrote the paper.
HFpEF affects millions of people around the world. In this condition, the heart muscle becomes stiff and cannot stretch properly to hold blood. This causes pressure to build up, leading to shortness of breath and swelling in the lungs, belly, or legs.
Doctors used to think that high blood pressure was the main cause of HFpEF. But now they believe it may be linked to fat deep inside the body, especially around the heart and organs.
The Adipokine Hypothesis explains that fat tissue releases special chemical messengers called adipokines. In healthy people, these chemicals help protect the heart and kidneys. But when there is too much fat, the chemicals change and start causing stress, inflammation, and scarring in the heart.
Some medicines can treat HFpEF by changing the way fat behaves, not by directly treating the heart. These include GLP-1 drugs like semaglutide and tirzepatide, which may help restore healthy fat signals.
The paper also says that BMI (body mass index) is not a good way to tell who has too much harmful fat. Instead, doctors should use the waist-to-height ratio. If a person’s waist is more than half their height, they may have too much internal fat—even if they don’t seem overweight.
Many people with HFpEF don’t know they have it. They may feel tired or out of breath but blame it on being out of shape. Dr. Packer says doctors should pay close attention to these symptoms, especially in people with a large waist.
Over 30 years ago, Dr. Packer introduced another major theory about heart failure that changed how doctors treated it. He hopes the new Adipokine Hypothesis will do the same for HFpEF.
Two more papers were also released that focus on related topics—how inflammation and tiny molecules from fat (called microRNAs) affect the heart in HFpEF.
The study is published in JACC: Heart Failure.
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